In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.

<h4>Objectives</h4>The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown.<h4>Methods</h4>In vitro time-kill studies were performed to evaluate synergism. Female BAL...

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Autores principales: Hee-Chang Jang, Su-Mi Choi, Hee Kyung Kim, Sung-Eun Kim, Seung-Ji Kang, Kyung-Hwa Park, Phil Youl Ryu, Tae-Hoon Lee, Young Ran Kim, Joon Haeng Rhee, Sook-In Jung, Hyon E Choy
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:97a95066ab3e4ce8b0039230fa9e10cd2021-11-25T06:10:21ZIn vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.1932-620310.1371/journal.pone.0101118https://doaj.org/article/97a95066ab3e4ce8b0039230fa9e10cd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24978586/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objectives</h4>The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown.<h4>Methods</h4>In vitro time-kill studies were performed to evaluate synergism. Female BALB/c mice were injected subcutaneously with 1×10(7) or 1×10(8) cfu of V. vulnificus. Antibiotic therapy was initiated at 2 h after inoculation in the following four therapy groups: cefotaxime; ciprofloxacin; cefotaxime-plus-ciprofloxacin; and cefotaxime-plus-minocycline. The cytotoxicity of V. vulnificus for HeLa cells was measured using the lactate dehydrogenase assay; rtxA1 transcription was measured in a transcriptional reporter strain using a β-galactosidase assay.<h4>Results</h4>In vitro time-kill assays exhibited synergism between cefotaxime and ciprofloxacin. In the animal experiments, the 96-h survival rate for the cefotaxime-plus-ciprofloxacin group (85%; 17/20) was significantly higher than that of the cefotaxime-plus-minocycline (35%; 7/20) and cefotaxime alone (0%; 0/20) groups (P<0.05 for both). Bacterial counts in the liver and spleen were significantly lower in the cefotaxime-plus-ciprofloxacin group 24 and 48 h after treatment, relative to the other groups. At sub-inhibitory concentrations, ciprofloxacin inhibited more effectively rtxA1 transcription and mammalian cell cytotoxicity than either minocycline or cefotaxime (P<0.05 for both).<h4>Conclusions</h4>Ciprofloxacin is more effective at reducing rtxA1 transcription and subsequent cytotoxicity than either minocycline or cefotaxime, and the combination of ciprofloxacin and cefotaxime was more effective in clearing V. vulnificus in vivo than previously used regimens. These data suggest that the combination of ciprofloxacin and cefotaxime is an effective option for the treatment of V. vulnificus sepsis in humans.Hee-Chang JangSu-Mi ChoiHee Kyung KimSung-Eun KimSeung-Ji KangKyung-Hwa ParkPhil Youl RyuTae-Hoon LeeYoung Ran KimJoon Haeng RheeSook-In JungHyon E ChoyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e101118 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hee-Chang Jang
Su-Mi Choi
Hee Kyung Kim
Sung-Eun Kim
Seung-Ji Kang
Kyung-Hwa Park
Phil Youl Ryu
Tae-Hoon Lee
Young Ran Kim
Joon Haeng Rhee
Sook-In Jung
Hyon E Choy
In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
description <h4>Objectives</h4>The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown.<h4>Methods</h4>In vitro time-kill studies were performed to evaluate synergism. Female BALB/c mice were injected subcutaneously with 1×10(7) or 1×10(8) cfu of V. vulnificus. Antibiotic therapy was initiated at 2 h after inoculation in the following four therapy groups: cefotaxime; ciprofloxacin; cefotaxime-plus-ciprofloxacin; and cefotaxime-plus-minocycline. The cytotoxicity of V. vulnificus for HeLa cells was measured using the lactate dehydrogenase assay; rtxA1 transcription was measured in a transcriptional reporter strain using a β-galactosidase assay.<h4>Results</h4>In vitro time-kill assays exhibited synergism between cefotaxime and ciprofloxacin. In the animal experiments, the 96-h survival rate for the cefotaxime-plus-ciprofloxacin group (85%; 17/20) was significantly higher than that of the cefotaxime-plus-minocycline (35%; 7/20) and cefotaxime alone (0%; 0/20) groups (P<0.05 for both). Bacterial counts in the liver and spleen were significantly lower in the cefotaxime-plus-ciprofloxacin group 24 and 48 h after treatment, relative to the other groups. At sub-inhibitory concentrations, ciprofloxacin inhibited more effectively rtxA1 transcription and mammalian cell cytotoxicity than either minocycline or cefotaxime (P<0.05 for both).<h4>Conclusions</h4>Ciprofloxacin is more effective at reducing rtxA1 transcription and subsequent cytotoxicity than either minocycline or cefotaxime, and the combination of ciprofloxacin and cefotaxime was more effective in clearing V. vulnificus in vivo than previously used regimens. These data suggest that the combination of ciprofloxacin and cefotaxime is an effective option for the treatment of V. vulnificus sepsis in humans.
format article
author Hee-Chang Jang
Su-Mi Choi
Hee Kyung Kim
Sung-Eun Kim
Seung-Ji Kang
Kyung-Hwa Park
Phil Youl Ryu
Tae-Hoon Lee
Young Ran Kim
Joon Haeng Rhee
Sook-In Jung
Hyon E Choy
author_facet Hee-Chang Jang
Su-Mi Choi
Hee Kyung Kim
Sung-Eun Kim
Seung-Ji Kang
Kyung-Hwa Park
Phil Youl Ryu
Tae-Hoon Lee
Young Ran Kim
Joon Haeng Rhee
Sook-In Jung
Hyon E Choy
author_sort Hee-Chang Jang
title In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
title_short In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
title_full In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
title_fullStr In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
title_full_unstemmed In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
title_sort in vivo efficacy of the combination of ciprofloxacin and cefotaxime against vibrio vulnificus sepsis.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/97a95066ab3e4ce8b0039230fa9e10cd
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